Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant CNS neoplasm whichprimarily occurs in children under three years of age. Due to poor outcomes with intense and toxicmultimodality treatment, new therapies are urgently needed. Histone deacetylase inhibitors (HDIs)have been evaluated as novel agents for multiple malignancies and have been shown to function asradiosensitizers. They act as epigenetic modifiers and lead to re-expression of inappropriatelyrepressed genes, proteins, and cellular functions. Due to the underlying chromatin remodeling genemutation in ATRT, HDIs are ideal candidates for therapeutic evaluation. To evaluate the role of HDIsagainst ATRT in vitro, we assessed the effect of drug treatment on proliferation, apoptosis, and geneexpression. Additionally, we examined HDI pretreatment as a radiosensitization strategy for ATRT.MTS and clonogenic assays demonstrated that HDI treatment significantly reduces the proliferativecapacity of BT-12 and BT-16 ATRT cells. Also, the HDI SNDX-275 was able to induce apoptosis in bothcell lines and induced p21Waf1/Cip1 protein expression as measured by Western blot. Evaluation ofdifferential gene expression by microarray and pathway analysis after HDI treatment demonstratedalterations of several key ATRT cellular functions. Finally, we showed that HDI pretreatmenteffectively potentiates the effect of ionizing radiation on ATRT cells as measured by clonogenic assay.These findings suggest that the addition of HDIs to ATRT therapy may prove beneficial, especiallywhen administered in combination with current treatment modalities such as radiation.
Histone deacetylase inhibition decreases proliferation and potentiates the effect of ionizing radiation in atypical teratoid/rhabdoid tumor cells.
Specimen part, Cell line
View SamplesUsing a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Age, Specimen part, Cell line, Subject
View SamplesUsing a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Age, Specimen part, Cell line, Subject
View SamplesInjury of skeletal muscle is a common occurence affecting millions worldwide. Injuries usually are not major incisions into daily life, however, the underlying health varies e. g. due to obesity. Obesity is usually accompanied by excessive and dysfunctional lipid depots, chronic low-grade inflammation as well as several co-morbidities, which are able to impair the regeneration of skeletal muscle.
Comparison of Fatty Acid and Gene Profiles in Skeletal Muscle in Normal and Obese C57BL/6J Mice before and after Blunt Muscle Injury.
Sex, Specimen part
View SamplesmDC and pDC exhibit distinct TLR expression pattern and differ in their responses to various TLR ligands. The goal of this study was to identify genes, that were differentally expressed between mDC and pDC as a means to determine how TLR signaling pathways operate. Suprisingly, expression of TLR-assoociated signaling proteins were found to be present at equivalent levels between mDC and pDC, despite differential expression of TLRs, and thus revealing insight into use of adaptor proteins that function as general regulators of TLR signaling pathways in both cell types.
A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Standard of hygiene and immune adaptation in newborn infants.
Sex
View SamplesThe prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Standard of hygiene and immune adaptation in newborn infants.
Sex
View SamplesThe prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Standard of hygiene and immune adaptation in newborn infants.
Sex
View SamplesTransfection of dsDNA into many mammalian cell types indues the production of type I interferons and interferon-stimulated genes. We performed an siRNA screen to identify genes involved in this innate immune response, and identified Abcf1.
Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach.
Specimen part
View SamplesWe used microarrays to determine which genes are upregulated by IFNbeta stimulation in 293T cells.
Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach.
Specimen part, Cell line, Treatment
View Samples